The overall objectives of this proposal are to use an already established SIV-infected rhesus macaque model to examine T-cell homeostasis and cytokine response in the intestinal mucosa of macaques infected with either pathogenic SIVmav 251 or attenuated (non-pathogenic) SIVmac 1A11. Changes occurring in the intestine will be compared to those occurring in peripheral lymph nodes and in blood. The specific aims of the proposal are to determine: (1) alterations in T cell homeostasis and cytokine response in intestinal mucosa during the early stages (primary acute and asymptomatic) of pathogenic SIVmac251; (2) alterations in T cell homeostasis and cytokine response in intestinal mucosa during the early stages of non-pathogenic SIV mac1A11 infection; (3) examine the effects of anti-retroviral therapy (PMPA) on the restoration of immune responses and intestinal lymphocyte subsets of chronically SIVmac251-infected animals. The investigators will test the following hypotheses: (A) The depletion of CD4 T cells and CD4/CD8 T cells in the intestinal mucosa during primary infection may alter the established T cell homeostasis and contribute to viral pathogenesis; the changes are reflected in the cytokine response of intestinal lymphocytes;(B) The alterations in T-cell homeostasis and cytokines that are generated in response to infection with SIVmac 251 can be distinguished from those changes that occur in response to infection with SIVmac 1A11. (C)Antiretroviral therapy may result in restoration of functioning T cell subsets; this restoration may not be reflected in the peripheral lymph nodes and blood. Viral loads will be measured by branched DNA signal amplification assay and in situ hybridization. Immunophenotypic analysis and evaluation of intracellular cytokine production following mitogenic or antigenic stimuli will be performed by flow cytometry. These studies are aimed at providing insights into the CD4 T cell depletion and altered T cell homeostasis in the GALT compared to the periphery.